Atherosclerosis: From Pathogenesis to Therapeutic Interventions

ABSTRACT Atherosclerosis is no longer viewed solely as a lipid‐storage disorder but rather as a complex multisystem inflammatory disease driven by interactions among the vascular, immune, metabolic, and nervous systems. This review integrates recent concepts, including trained immunity, the neuroimmune cardiovascular interface, vascular cell plasticity, and the microbiome–vascular axis, that reshape the understanding of plaque initiation, progression, and instability. We summarize how established lipid‐lowering, antidiabetic, antihypertensive, and revascularization strategies influence atherosclerotic disease and discuss emerging interventions, including RNA therapeutics, anti‐inflammatory agents, gene therapy, and cell‐based approaches. Key ongoing clinical trials that may clarify the cardiovascular benefits and safety of these strategies are also reviewed. Despite therapeutic advances, residual cardiovascular risk persists because of limitations in animal models, sex‐related differences in plaque phenotype, and the lack of clinically applicable biomarkers. Nanotechnology, human microphysiological systems, spatial multiomics, and artificial intelligence may help bridge these translational gaps. Successful clinical implementation will nevertheless require biomarker‐guided patient selection, rational combination therapy, validated surrogate endpoints, long‐term safety assessment, and attention to health economics. In summary, these advances will shape future translational research and clinical trial design, ultimately advancing personalized management of atherosclerosis.